Amlodipine with Erythromycin Interaction Details

Brand Names Associated with Amlodipine

Brand Names Associated with Erythromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 03, 2024

Interaction Effect

Increased amlodipine exposure

Interaction Summary

Coadministration of amlodipine with moderate and strong CYP3A inhibitors, such as erythromycin, results in increased systemic exposure to amlodipine. In a pharmacokinetic study of elderly hypertensive patients, coadministration of diltiazem (a CYP3A inhibitor) with amlodipine resulted in a 60% increase in amlodipine systemic exposure[1]. Additionally, coadministration of erythromycin with a calcium channel blocker (including amlodipine) was associated with significantly increased short-term risk of hospital admission within 7 days for hypotension or shock in a cohort study of geriatric patients [2]. Dose reduction of amlodipine may be required if symptoms of hypotension and edema occur with coadministration of CYP3A inhibitors [1]. If clinically appropriate, consider the use of azithromycin (which does not inhibit CYP3A4) if treatment with a macrolide is required [2].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Coadministration of amlodipine with moderate and strong CYP3A inhibitors, such as erythromycin, results in increased systemic exposure to amlodipine. Dose reduction of amlodipine may be required if symptoms of hypotension and edema occur with coadministration of CYP3A inhibitors[1]. If clinically appropriate, consider the use of azithromycin (which does not inhibit CYP3A4) if treatment with a macrolide is required [2].

Mechanism Of Interaction

Inhibition of CYP3A-mediated metabolism of amlodipine

Literature Reports

A) Coadministration of macrolide antibiotics erythromycin or clarithromycin with a calcium channel blocker was associated with significantly increased short-term risk of hospital admission within 7 days for hypotension or shock ([OR, 5.8; 95% CI, 2.25 to 14.98] or [OR, 3.7; 95% CI, 2.26 to 6.06]) in a case-crossover cohort study of geriatric patients (N=7100); there was no significant risk associated with azithromycin. In a stratified analysis of dihydropyridine calcium channel blockers (amlodipine, felodipine, NIFEdipine), the results remained significant for coadministration of erythromycin or clarithromycin. Calcium channel blocker treatment included diltiazem (40%), amlodipine (29.6%), NIFEdipine (19.4%), verapamil (8%), or felodipine (3%). The findings suggest that erythromycin and clarithromycin potentiate calcium channel blockers (CYP3A4 substrates) by inhibiting CYP3A4; azithromycin does not inhibit CYP3A4 [2].

B) In a pharmacokinetic study of elderly hypertensive patients, coadministration of diltiazem (a CYP3A inhibitor) 180 mg daily with amlodipine 5 mg resulted in a 60% increase in amlodipine systemic exposure [1].

References

1 ) Product Information: EXFORGE oral tablets, amlodipine valsartan oral tablets. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2019.

2 ) Wright AJ, Gomes T, Mamdani MM, et al: The risk of hypotension following co-prescription of macrolide antibiotics and calcium-channel blockers. CMAJ 2011; 183(3):303-307.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

Amlodipine Overview

• Amlodipine is used alone or in combination with other medications to treat high blood pressure in adults and children 6 years and older. It is also used to treat certain types of angina (chest pain) and coronary artery disease (narrowing of the blood vessels that supply blood to the heart). Amlodipine is in a class of medications called calcium channel blockers. It lowers blood pressure by relaxing the blood vessels so the heart does not have to pump as hard. It controls chest pain by increasing the supply of blood to the heart. If taken regularly, amlodipine controls chest pain, but it does not stop chest pain once it starts. Your doctor may prescribe a different medication to take when you have chest pain.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

Erythromycin Overview

• Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections. It also is used to prevent recurrent rheumatic fever. Erythromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as erythromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.